Systems and methods for creating and viewing three dimensional virtual slides

ABSTRACT

Systems and methods for creating and viewing three dimensional virtual slides are provided. One or more microscope slides are positioned in an image acquisition device that scans the specimens on the slides and makes two dimensional images at a medium or high resolution. This two dimensional images are provided to an image viewing workstation where they are viewed by an operator who pans and zooms the two dimensional image and selects an area of interest for scanning at multiple depth levels (Z-planes). The image acquisition device receives a set of parameters for the multiple depth level scan, including a location and a depth. The image acquisition device then scans the specimen at the location in a series of Z-plane images, where each Z-plane image corresponds to a depth level portion of the specimen within the depth parameter.

RELATED APPLICATION

The present application claims the benefit of U.S. provisional patentapplication Ser. No. 60/574,991 filed on May 27, 2004, which isincorporated herein by reference in its entirety.

BACKGROUND

1. Field of the Invention

The present invention generally relates to creating and viewing virtualmicroscope slide images and more particularly relates to the creatingand viewing of three dimensional virtual microscope slide images.

2. Related Art

Conventional microscopes, using mechanical focusing mechanisms ofsufficient quality, are easily focused by an observer. The feedback loopbetween the eye/brain and the fingers is extremely rapid and accurate.If any part of the feedback loop is impaired, however, the process ofobtaining perfect focus becomes extremely difficult, time consuming andeven inaccurate. These impairments may arise from poor optical quality,insufficient or incorrect illumination, inaccuracies in the focusingmechanism, or even due to poor visual acuity of the operator.

More recently, conventional computer implemented microscope systems haveprovided the ability to remotely access high resolution images ofmicroscope slides for a number of years. Devices capable of creatingsuch images fall into two broad categories: (1) remote controlled (orrobotic) microscopes; and (2) imagers, which create some type ofelectronic or photographic image of some, or all, of the specimen. Eachtype has its advantages and disadvantages, many of which are unique tothe particular application.

Remote controlled microscopes, which essentially replace the operator'seye with an electronic camera, allow the operator to control the focusplane of the camera. This capability is particularly advantageous whenviewing thick specimens. However, the optical field of view at moderateor high resolution is extremely small due to a limited number of camerapixels. This makes it very difficult and time consuming to view anentire specimen on a microscope slide even at moderate magnification.

Conventional imaging systems are capable of creating large enough imagesto capture an entire specimen at moderate or high magnification. Theseimages are called virtual microscope slides or virtual slides. Becauseof their extremely large size, virtual slides are usually limited to asingle focus level (“Z-plane”). Many types of microscope specimens arevery thin so a single Z-plane virtual slide is sufficient. Other typesof microscope specimens, however, are thicker than the depth of field ofthe objective lens.

Remote controlled microscopes additionally suffer from an even moredegrading effect—time lag. Because a remotely controlled microscope ismerely a microscope with motorized stages for positioning and focusingthe specimen, and a camera to transmit images to a remote user, if theimage being displayed to the user is delayed by even a small fraction ofa second, the feedback loop will be frustrating, if not nearlyimpossible to use. The user, viewing the electronic image on a remotemonitor, will attempt to converge on the optimally focused image, onlyto find that the image continues to zoom after he has attempted to stopat the best focus. The process must then be repeated in smaller andsmaller iterations, at slower and slower speeds until finally, asatisfactory focus is obtained. Time lag in conventional systems, inparticular as it applies to a networked attached device making use of aninternet connection, has several contributing causes. One cause can betraced to the design of the device itself. Poor system design, andinefficient data processing methods can add significantly to theperceived sluggishness of conventional systems.

Two other factors are more serious in that they cannot always becontrolled by the designer. The first is bandwidth. Bandwidth refers tothe capacity of a network to transmit data, or in the case of a roboticmicroscope, the imagery being displayed to the operator, and the controlsignals returning to the device to affect its position and focus. Lownetwork bandwidth limits the update rate of the image on the videodisplay. Fortunately, increased bandwidth may be purchased at greaterexpense, effectively solving this problem. The second problem, calledlatency, is not so easily solved. Latency is simply the delay timebetween network nodes. Even fast networks have some degree of latency.Delays, often on the order of seconds, are not uncommon over theInternet. Latency is the Achilles heel of real-time feedback controlsystems.

What is needed is a remote device that appears to the user as anextremely responsive, high bandwidth, low latency, remote controlledmicroscope that does not suffer from the limitations of the conventionalsystems described above.

SUMMARY

Accordingly, certain embodiments are described herein that providesystems and methods that allow users to locally or remotely interactwith a microscope slide image acquisition device or image data serverdevice for responsive, high bandwidth, low latency acquisition andviewing of virtual slide images in multiple Z-planes. The systems andmethods described herein combine the advantages of remote controlledmicroscopes and microscope imaging systems and provide the ability toscan large regions of a specimen on a microscope slide at highresolution, as well as the ability for an operator to quickly viewselected areas of interest and control the focus depth within a thickspecimen.

One aspect of the invention is a computer implemented method forcreating and viewing three dimensional virtual microscope slides. Amicroscope slide is positioned in an image acquisition device that iscapable of scanning the slide to create a digital image of the specimenon the slide. The specimen is then scanned into a two dimensional imageat a medium or high resolution. This two dimensional image is providedto an image viewing workstation where it can be reviewed by an operator.The operator can pan and zoom the two dimensional image at the imageviewing workstation and select an area of interest for scanning atmultiple depth levels (Z-planes). The image acquisition device receivesa set of Z-stack parameters including a location and a depth and thenscans a series of Z-plane images, where each Z-plane image correspondsto a portion of the specimen within the depth parameter.

BRIEF DESCRIPTION OF THE DRAWINGS

The details of the present invention, both as to its structure andoperation, may be gleaned in part by study of the accompanying drawings,in which like reference numerals refer to like parts, and in which:

FIG. 1 is a block diagram illustrating an example networked systemaccording to an embodiment of the present invention;

FIG. 2 is a side view of an example microscope slide with a specimenaccording to an embodiment of the present invention;

FIG. 3 is a block diagram illustrating an example three dimensionalZ-stack according to an embodiment of the present invention;

FIG. 4 is flow diagram illustrating an example high level process forcreating a three dimensional virtual microscope slide according to anembodiment of the present invention;

FIG. 5 is a flow diagram illustrating an example process for creating athree dimensional virtual microscope slide according to an embodiment ofthe present invention;

FIG. 6 is a block diagram illustrating an example user interface forcreating a three dimensional virtual slide according to an embodiment ofthe present invention;

FIG. 7 is a block diagram illustrating an example scan path for an imageacquisition device over a specimen having varying thickness according toan embodiment of the present invention;

FIG. 8 is a block diagram illustrating an example three dimensionalvirtual slide that results from a three dimensional scan of the specimenshown in FIG. 7 according to an embodiment of the present invention;

FIG. 9 is a flow diagram illustrating an example process for viewingthree dimensional virtual slides according to an embodiment of thepresent invention; and

FIG. 10 is a block diagram illustrating an exemplary computer system asmay be used in connection with various embodiments described herein.

DETAILED DESCRIPTION

Certain embodiments as disclosed herein provide for systems and methodsfor creating and viewing three dimensional virtual slides. For example,one method as disclosed herein allows for one or more microscope slidesto be positioned in an image acquisition device that scans the specimenson the slides and makes two dimensional images at a medium or highresolution. Alternatively, the entire specimens can be captured at oncein a low resolution “macro” image. These high or low resolution twodimensional images are provided to an image viewing workstation wherethey are viewed by an operator who pans and zooms the two dimensionalimage and selects an area of interest for scanning at multiple depthlevels (Z-planes). The image acquisition device receives a set ofparameters for the multiple depth level scan, including a location and adepth. The image acquisition device then scans the specimen at thelocation in a series of Z-plane images, where each Z-plane imagecorresponds to a depth level portion of the specimen within the depthparameter. After reading this description it will become apparent to oneskilled in the art how to implement the invention in various alternativeembodiments and alternative applications. However, although variousembodiments of the present invention will be described herein, it isunderstood that these embodiments are presented by way of example only,and not limitation. As such, this detailed description of variousalternative embodiments should not be construed to limit the scope orbreadth of the present invention as set forth in the appended claims.

FIG. 1 is a block diagram illustrating an example networked system 10according to an embodiment of the present invention. In the illustratedembodiment, the system 10 comprises an image acquisition device (“LAD”)20, an image data server (“IDS”) 30, and an image viewing workstation(“IVW”) 40. Each of these devices is associated with a respective datastorage area 25, 35, and 45, and each of the devices is communicativelycoupled to the others via a network 50. Alternatively, the devices maybe directly connected to each other or connected to each other viaseparate networks. In one embodiment, two or more of the devices may bemodularly integrated into the same physical device, in which case thecommunication between functional modules may take place throughinter-process communication, shared memory, common files or the like.

The IAD 20 comprises hardware and software which can acquiretwo-dimensional images from microscope slides. The IAD 20 may acquireimages from the slide at any location within the slide (X,Y) and at anyfocal depth (Z).

FIG. 1 is a block diagram illustrating an example networked system 10according to an embodiment of the present invention. In the illustratedembodiment, the system 10 comprises an image acquisition device (“IAD”)20, an image data server (“IDS”) 30, and an image viewing workstation(“IVW”) 40. Each of these devices is associated with a respective datastorage area 25, 35, and 45, and each of the devices is communicativelycoupled to the others via a network 50. Alternatively, the devices maybe directly connected to each other or connected to each other viaseparate networks. In one embodiment, two or more of the devices may bemodularly integrated into the same physical device, in which case thecommunication between functional modules may take place throughinter-process communication, shared memory, common files or the like.

Specimens on a microscope slide usually have an overall dimension ofbetween 10 and 30 mm per side. For example, a typical sample could covera region of 20×15 mm. Such a sample, when imaged fully at a resolutionof 0.25 microns per pixel (i.e., 40×), yields an image that has80,000×60,000 pixels. Accurately obtaining full slide images istechnically difficult, but may be accomplished with instruments such asthe Aperio ScanScope® that is described in detail in U.S. Pat. No.6,711,283 (Soenksen), which is incorporated herein by reference in itsentirety.

The IDS 30 comprises a server computer and software which stores andenables access to two- and three-dimensional images acquired by the IAD.The IDS can be located near the IAD 20 on a local-area network. In analternative embodiment it may be desirable for the IDS 30 to be remotefrom the IAD 20 and connected via a wide-area network.

The IVW 40 comprises a personal computer and software which can displaytwo and three dimensional images acquired by the IAD 20 and retrievedfrom the IDS 30. The IVW 40 may be located across a local area networkor wide area network from the IAD 20 and IDS 30, using standard computernetwork technology such as TCP/IP. The user at an IVW 40 directs the IAD20 to capture image data of the specimen on a microscope slide, andviews it interactively. The captured image data are stored on the IDS30, from which they may be later viewed using an IVW 40.

The network 50 may be a local area network, a wide area network, a wiredor wireless network, or any combination of networks. On such combinationof networks is commonly referred to as the Internet. Network 50 may bethe Internet or any sub-combination of the networks that comprise theInternet. Network 50 may also be a private network or a public networkor any combination of networks.

FIG. 2 is a side view of an example microscope slide with a specimenaccording to an embodiment of the present invention. In the illustratedembodiment, the slide 110 supports a sample of tissue 100 (also referredto herein as a specimen). The tissue 100 may be any type of microscopeslide specimen such as blood or other substances.

Although tissue samples such as tissue 100 on a microscope slide appearflat, at the micron and sub-micron resolution level they actually have aconsiderable amount of variation in thickness. The thickness of samplescan vary from 0.5 micron to 10 microns. In some cases it is medicallyimportant to view samples three-dimensionally, by focusing the 0.5/1.0micron focal depth through the specimen, e.g., an area of a specimenthat is 10 microns thick. This is typically accomplished by capturingmultiple images at the same location on the specimen but at varyingfocal depths. A set of images acquired from one location on the specimenat different focus depths is called a “Z-stack” and each individualimage in the Z-stack is called a “Z-plane.”

FIG. 3 is a block diagram illustrating an example three dimensionalZ-stack 200 according to an embodiment of the present invention. In theillustrated embodiment, the Z-stack 200 is taken from a location on thespecimen that is 10 microns thick (see corresponding area in FIG. 2). Inthe illustrated embodiment, the Z-stack 200 comprises 10 Z-planes 210.In this particular embodiment, the focus depth of the objective lens is1 micron so that 10 contiguous Z-planes are captured and collectivelycover the entire 10 micron thickness of the specimen.

In alternative embodiments, the depth of a single Z-plane may be more orless than 1 micron and the various Z-planes maybe be spaced apart ratherthan being contiguous.

The lateral (X,Y) dimensions of each Z-plane image in a Z-stack aretypically determined by the acquisition hardware, such as the size of acamera's CCD array. In one embodiment the dimensions of the CCD arraymay be 2048×1536 pixels. A Z-plane image may also be a combination ofseveral fields of view combined together. The number and spacing of theimages in a Z-stack are configurable, and dependent upon the sample typeand nature of the medical application. In one embodiment, a typicalZ-stack contains 5-10 images spaced 0.25-1.0 micron apart.

FIG. 4 is flow diagram illustrating an example high level process forcreating a three dimensional virtual microscope slide according to anembodiment of the present invention. This procedure may be carried outby the system shown and described with respect to FIG. 1. Initially, instep 250 the IAD captures a two dimensional image of the specimen on themicroscope slide. Next, in step 255 this image is presented to a user ofthe UVW. The imagery data going to the IVW may route through the IDSwhere the imagery data are first stored as a virtual slide or portion ofa virtual slide, then presented to the user.

The user may pan and zoom and otherwise review the two dimensionalimage(s) via the IVW to identify an area of interest for threedimensional image capture. In step 260, the IAD receives a location torevisit for three dimensional image capture. In one embodiment, the IVWsends the location information directly to the IAD. At this point, instep 265, the IAD may optionally rescan the identified location at ahigher resolution and then present the higher resolution area to theuser for review. For example, in one embodiment, the initial twodimensional scan may be a low resolution scan that requires a review ata higher resolution prior to a decision being made about whether tocapture a Z-stack at that location. Alternatively, the initial scan maybe at a sufficiently high resolution (e.g., 20×) to make thatdetermination. In such an alternative embodiment, optional step 265 canbe skipped.

Next, the IAD receives three dimensional scan parameters, as illustratedin step 270. These parameters may include length and width identifiersthat uniquely describe a region of the specimen in coordinates thatrelate to the stage of the IAD upon which the microscope slide sits.Other parameters may also include the number of Z-planes desired in theZ-stack. Additionally, the parameters may include the desired spacingbetween Z-planes in the Z-stack. Additional information may also includethe desired scanning resolution (e.g., 20×, 40×, 100×). Other parametersmay also be provided.

Finally, in step 275 the IAD captures the various Z-planes in theZ-stack. These Z-planes can then be sent to the IDS for storage alongwith the two dimensional image as part of the same virtual slide. In oneembodiment, the capturing of the Z-stack proceeds down the Z-planelevels as shown in FIG. 3. For example, the IAD may first captureZ-plane 1 and then move the objective lens relative to the stage (orvice-versa) and capture Z-plane 2 and so forth until all of the Z-planesin the Z-stack have been captured.

FIG. 5 is a flow diagram illustrating an example process for creating athree dimensional virtual microscope slide according to an embodiment ofthe present invention. This procedure may be carried out by the systemshown and described with respect to FIG. 1. Initially, in step 305 theIVW receives an instruction to initiate a “revisit” three dimensionalscan. The IVW next, in step 310, obtains and presents the contents ofthe subject virtual slide to the user. This may be done throughinteractions directly with the IAD or it may be achieved throughinteractions with the IDS or both. After providing the user with thevirtual slide for viewing, the IVW then works together with the IDS torespond to pan and zoom requests in step 315 as the user views thespecimen in the virtual slide. Next, in step 320, the IVW receives thethree dimensional scan parameters and sends the parameters to the IAD.The three dimensional scan parameters may include the location of thearea to be revisited for Z-stack capture, the length and width of thearea, the number of Z-planes to be captured in the Z-stack, the spacingbetween Z-planes in the Z-stack, the resolution of the Z-plane images,and the total depth of tissue to be included in the Z-stack, just toname a few. Additional parameters may also be provided to increase theaccuracy and sufficiency of the Z-stack to be scanned.

Next, in step 320, the IAD captures the Z-plane images in the Z-stackand sends the images in the Z-stack to the IDS for storage as part ofthe virtual microscope slide. The IDS, in turn, may then send theZ-stack imagery data to the IVW as part of the virtual slide where it ispresented as a Z-stack to the user, as shown in step 330.

FIG. 6 is a block diagram illustrating an example user interface forcreating a three dimensional virtual slide according to an embodiment ofthe present invention. In the illustrated embodiment, a rectangular area350 is shown that comprises an area of a specimen on a microscope to berevisited for three dimensional image capture. The rectangular area hasa length 360 and a width 355, and a crosshair 365 that identifies thelocation of the center of the region to be scanned into a Z-stack. Inone embodiment, the user may drag the rectangle using a mouse on thescreen of the IVW to specify the area of interest. After the rectangleis created by the user, the IVW may calculate the actual length andwidth and location for the area to be scanned into a Z-stack. Theseparameters may then be sent to the IAD for to facilitate image capturefor the Z-stack.

Additionally, in the illustrated embodiment the user is presented with aselection of icons 370, 375, and 380 that be used to select the size ofthe rectangular region 350, to select the depth of the region to bescanned into the Z-stack, and to select the spacing between individualZ-planes in the Z-stack. Advantageously, these selections by the usercan also be sent to the IAD as parameters for facilitating image capturefor the Z-stack. Alternative user interfaces may also be employed tocarry out the function of user interaction for identifying an area ofinterest to scan into a Z-stack.

FIG. 7 is a block diagram illustrating an example scan path for an imageacquisition device over a specimen having varying thickness according toan embodiment of the present invention. In the illustrated embodiment,an objective lens 400 is shown over a tissue sample 100 on a microscopeslide 110. The objective lens, when scanning the tissue 100 travelsalong a scan path 410 and passes over the tissue 100. The tissue 100 maybe highly uneven (e.g., as seen through a 40× objective lens at themicron level) and comprises several thick regions 420, 430, and 440. Forpurposes of this example, the thick region 420 is 10 microns, the thickregion 430 is 5 microns, and the thick region 440 is also 6 microns.These thick regions are separated by valleys in the tissue that are notthick and, for example, are 0.5 microns thick and 1 micron thick.

During the initial scan of the tissue 100, a two dimensional image iscreated. This two dimensional image is shown as image 450 in FIG. 8.FIG. 8 is a block diagram illustrating an example three dimensionalvirtual slide that results from a three dimensional scan of the tissue100 shown in FIG. 7 according to an embodiment of the present invention.Also shown in FIG. 8 are the resulting Z-stacks 425, 435, and 445, eachof which have a plurality of Z-planes such as Z-planes 460.

Z-stack 425 corresponds to thick region 420 and comprises 10 Z-planes.In this example, the objective lens 400 has a focus depth of 1 micron sothat 10 contiguous Z-planes 460 cover the entire thickness of the region420. Z-stack 435 corresponds to thick region 430 and similarly comprises5 Z-planes. Z-stack 445 corresponds to thick region 440 and alsocomprises 5 Z-planes.

In the illustrated embodiment shown in FIG. 8, the Z-plane correspondingto the two dimensional image 450 is located in the middle of each of theZ-stacks. This is because when the example Z-stacks were captured, themiddle depth of the Z-stack was set for the same depth at which theinitial two dimensional image 450 was captured. Accordingly, to arriveat the virtual slide shown in FIG. 8, an initial two dimensional image450 was captured by the IAD, the user identified thick regions 420, 430,and 440 for Z-stack capture, and when the IAD captured those Z-stacks,the depth level of the Z-plane in the middle of the Z-stack was set atthe same level at which the two dimensional image was captured.

In alternative embodiments, the various Z-planes of a Z-stack may all beset below the depth level of the original two dimensional image.Alternatively, the various Z-planes of a Z-stack may all be set abovethe depth level of the original two dimensional image. Various differentcalibrations may also be used for the planes in a Z-stack in order tooptimize the capture of imagery data of actual tissue for inclusion inthe virtual slide image.

FIG. 9 is a flow diagram illustrating an example process for viewingthree dimensional virtual slides according to an embodiment of thepresent invention. This procedure may be carried out by the system shownand described with respect to FIG. 1 and in one embodiment may onlyrequire the IDS and IVW devices. Initially, in step 500 the IDS receivesa viewing instruction from the IVW. In response, the IDS obtains therequested virtual slide from a data storage area (could be local orremote) and provides the virtual slide to the IVW. Next, in step 505 theIVW presents the virtual slide imagery data to the user. Note thatalthough the virtual slide is presented to the user via the IVW, only asubset of the entire virtual slide imagery data is presented at anytime. For example, a thumbnail image of the entire virtual slide may bepresented simultaneously with one or two additional views of the imagerydata at different resolutions.

Once the virtual slide is being presented to the user, the IVW and IDSwork in concert to respond to pan and zoom commands from the user, asshown in step 510. This allows the user to view all areas of thespecimen at low and high magnification and importantly at a diagnosticresolution. During the pan and zoom interaction with the user, the IVWand IDS monitor the areas of the specimen that are being viewed by theuser. When an area of the specimen that includes a Z-stack is beingviewed, as determined in step 515, the IVW provides the user with accessto the Z-plane images of the Z-stack, as shown in step 520.

In one embodiment, the user may be notified of the presence of a Z-stackby a visual cue. For example, the imagery data may be supplemented withan overlay that identifies a Z-stack or a new menu may appear or aninformational window may pop-up to notify the user that a Z-stack ispresent. Many other notification schemes may also be employed.

Advantageously, when a user encounters a Z-stack, the IVW may providethe user with the ability to select each Z-plane in the Z-stack forindividual viewing. Furthermore, intermediate focus depth levels can beinterpolated by the IVW to provide the user with continuous imagery datafor the entire specimen in the area of the Z-stack. Accordingly,although a finite number of Z-plane images are captured as part of theZ-stack, the user can zoom through a nearly infinite number of focusdepths. This ability provides the user with the complete ability toexamine a specimen as if using a conventional microscope.

FIG. 10 is a block diagram illustrating an exemplary computer system 550that may be used in connection with the various embodiments describedherein. For example, the computer system 550 may be used in conjunctionwith an image acquisition device, an image data server, or an imageviewing workstation. However, other computer systems and/orarchitectures may be used, as will be clear to those skilled in the art.

The computer system 550 preferably includes one or more processors, suchas processor 552. Additional processors may be provided, such as anauxiliary processor to manage input/output, an auxiliary processor toperform floating point mathematical operations, a special-purposemicroprocessor having an architecture suitable for fast execution ofsignal processing algorithms (e.g., digital signal processor), a slaveprocessor subordinate to the main processing system (e.g., back-endprocessor), an additional microprocessor or controller for dual ormultiple processor systems, or a coprocessor. Such auxiliary processorsmay be discrete processors or may be integrated with the processor 552.

The processor 552 is preferably connected to a communication bus 554.The communication bus 554 may include a data channel for facilitatinginformation transfer between storage and other peripheral components ofthe computer system 550. The communication bus 554 further may provide aset of signals used for communication with the processor 552, includinga data bus, address bus, and control bus (not shown). The communicationbus 554 may comprise any standard or non-standard bus architecture suchas, for example, bus architectures compliant with industry standardarchitecture (“ISA”), extended industry standard architecture (“EISA”),Micro Channel Architecture (“MCA”), peripheral component interconnect(“PCI”) local bus, or standards promulgated by the Institute ofElectrical and Electronics Engineers (“IEEE”) including IEEE 488general-purpose interface bus (“GPIB”), IEEE 696/S-100, and the like.

Computer system 550 preferably includes a main memory 556 and may alsoinclude a secondary memory 558. The main memory 556 provides storage ofinstructions and data for programs executing on the processor 552. Themain memory 556 is typically semiconductor-based memory such as dynamicrandom access memory (“DRAM”) and/or static random access memory(“SRAM”). Other semiconductor-based memory types include, for example,synchronous dynamic random access memory (“SDRAM”), Rambus dynamicrandom access memory (“RDRAM”), ferroelectric random access memory(“FRAM”), and the like, including read only memory (“ROM”).

The secondary memory 558 may optionally include a hard disk drive 560and/or a removable storage drive 562, for example a floppy disk drive, amagnetic tape drive, a compact disc (“CD”) drive, a digital versatiledisc (“DVD”) drive, etc. The removable storage drive 562 reads fromand/or writes to a removable storage medium 564 in a well-known manner.Removable storage medium 564 may be, for example, a floppy disk,magnetic tape, CD, DVD, etc.

The removable storage medium 564 is preferably a computer readablemedium having stored thereon computer executable code (i.e., software)and/or data. The computer software or data stored on the removablestorage medium 564 is read into the computer system 550 as electricalcommunication signals 578.

In alternative embodiments, secondary memory 558 may include othersimilar means for allowing computer programs or other data orinstructions to be loaded into the computer system 550. Such means mayinclude, for example, an external storage medium 572 and an interface570. Examples of external storage medium 572 may include an externalhard disk drive or an external optical drive, or and externalmagneto-optical drive.

Other examples of secondary memory 558 may include semiconductor-basedmemory such as programmable read-only memory (“PROM”), erasableprogrammable read-only memory (“EPROM”), electrically erasable read-onlymemory (“EEPROM”), or flash memory (block oriented memory similar toEEPROM). Also included are any other removable storage units 572 andinterfaces 570, which allow software and data to be transferred from theremovable storage unit 572 to the computer system 550.

Computer system 550 may also include a communication interface 574. Thecommunication interface 574 allows software and data to be transferredbetween computer system 550 and external devices (e.g. printers),networks, or information sources. For example, computer software orexecutable code may be transferred to computer system 550 from a networkserver via communication interface 574. Examples of communicationinterface 574 include a modem, a network interface card (“NIC”), acommunications port, a PCMCIA slot and card, an infrared interface, andan IEEE 1394 fire-wire, just to name a few.

Communication interface 574 preferably implements industry promulgatedprotocol standards, such as Ethernet IEEE 802 standards, Fiber Channel,digital subscriber line (“DSL”), asynchronous digital subscriber line(“ADSL”), frame relay, asynchronous transfer mode (“ATM”), integrateddigital services network (“ISDN”), personal communications services(“PCS”), transmission control protocol/Internet protocol (“TCP/IP”),serial line Internet protocol/point to point protocol (“SLIP/PPP”), andso on, but may also implement customized or non-standard interfaceprotocols as well.

Software and data transferred via communication interface 574 aregenerally in the form of electrical communication signals 578. Thesesignals 578 are preferably provided to communication interface 574 via acommunication channel 576. Communication channel 576 carries signals 578and can be implemented using a variety of wired or wirelesscommunication means including wire or cable, fiber optics, conventionalphone line, cellular phone link, wireless data communication link, radiofrequency (RF) link, or infrared link, just to name a few.

Computer executable code (i.e., computer programs or software) is storedin the main memory 556 and/or the secondary memory 558. Computerprograms can also be received via communication interface 574 and storedin the main memory 556 and/or the secondary memory 558. Such computerprograms, when executed, enable the computer system 550 to perform thevarious functions of the present invention as previously described.

In this description, the term “computer readable medium” is used torefer to any media used to provide computer executable code (e.g.,software and computer programs) to the computer system 550. Examples ofthese media include main memory 556, secondary memory 558 (includinghard disk drive 560, removable storage medium 564, and external storagemedium 572), and any peripheral device communicatively coupled withcommunication interface 574 (including a network information server orother network device). These computer readable mediums are means forproviding executable code, programming instructions, and software to thecomputer system 550.

In an embodiment that is implemented using software, the software may bestored on a computer readable medium and loaded into computer system 550by way of removable storage drive 562, interface 570, or communicationinterface 574. In such an embodiment, the software is loaded into thecomputer system 550 in the form of electrical communication signals 578.The software, when executed by the processor 552, preferably causes theprocessor 552 to perform the inventive features and functions previouslydescribed herein.

Various embodiments may also be implemented primarily in hardware using,for example, components such as application specific integrated circuits(“ASICs”), or field programmable gate arrays (“FPGAs”). Implementationof a hardware state machine capable of performing the functionsdescribed herein will also be apparent to those skilled in the relevantart. Various embodiments may also be implemented using a combination ofboth hardware and software.

Furthermore, those of skill in the art will appreciate that the variousillustrative logical blocks, modules, circuits, and method stepsdescribed in connection with the above described figures and theembodiments disclosed herein can often be implemented as electronichardware, computer software, or combinations of both. To clearlyillustrate this interchangeability of hardware and software, variousillustrative components, blocks, modules, circuits, and steps have beendescribed above generally in terms of their functionality. Whether suchfunctionality is implemented as hardware or software depends upon theparticular application and design constraints imposed on the overallsystem. Skilled persons can implement the described functionality invarying ways for each particular application, but such implementationdecisions should not be interpreted as causing a departure from thescope of the invention. In addition, the grouping of functions within amodule, block, circuit or step is for ease of description. Specificfunctions or steps can be moved from one module, block or circuit toanother without departing from the invention.

Moreover, the various illustrative logical blocks, modules, and methodsdescribed in connection with the embodiments disclosed herein can beimplemented or performed with a general purpose processor, a digitalsignal processor (“DSP”), an ASIC, FPGA or other programmable logicdevice, discrete gate or transistor logic, discrete hardware components,or any combination thereof designed to perform the functions describedherein. A general-purpose processor can be a microprocessor, but in thealternative, the processor can be any processor, controller,microcontroller, or state machine. A processor can also be implementedas a combination of computing devices, for example, a combination of aDSP and a microprocessor, a plurality of microprocessors, one or moremicroprocessors in conjunction with a DSP core, or any other suchconfiguration.

Additionally, the steps of a method or algorithm described in connectionwith the embodiments disclosed herein can be embodied directly inhardware, in a software module executed by a processor, or in acombination of the two. A software module can reside in RAM memory,flash memory, ROM memory, EPROM memory, EEPROM memory, registers, harddisk, a removable disk, a CD-ROM, or any other form of storage mediumincluding a network storage medium. An exemplary storage medium can becoupled to the processor such the processor can read information from,and write information to, the storage medium. In the alternative, thestorage medium can be integral to the processor. The processor and thestorage medium can also reside in an ASIC.

The above description of the disclosed embodiments is provided to enableany person skilled in the art to make or use the invention. Variousmodifications to these embodiments will be readily apparent to thoseskilled in the art, and the generic principles described herein can beapplied to other embodiments without departing from the spirit or scopeof the invention. Thus, it is to be understood that the description anddrawings presented herein represent a presently preferred embodiment ofthe invention and are therefore representative of the subject matterwhich is broadly contemplated by the present invention. It is furtherunderstood that the scope of the present invention fully encompassesother embodiments that may become obvious to those skilled in the artand that the scope of the present invention is accordingly limited bynothing other than the appended claims.

1. A system for creating and viewing three dimensional virtualmicroscope slides, comprising: an image acquisition device configured toscan a microscope slide and create a digital image of a specimen on themicroscope slide; an image data server communicatively coupled with theimage acquisition device, the image data server configured to receivevirtual microscope slide images from the image acquisition device, storethe virtual microscope slide images, and provide the virtual microscopeslide images upon request; an image viewing workstation communicativelycoupled with the image acquisition device and the image data server, theimage viewing workstation configured to display a two dimensional imageof a specimen on a microscope slide in the image acquisition device,receive commands from an operator, and in cooperation with the imagedata server, allow the operator to pan said two dimensional image; theimage viewing workstation further configured to receive a set of threedimensional scan parameters from the operator, said set includinglocation, length, width, depth, number of Z-planes, and spacing betweenZ-planes and in response to receiving said parameters, instruct theimage acquisition device to capture a Z-stack of images corresponding tosaid parameters from the specimen on the microscope slide; wherein theimage data server is further configured to store said Z-stack of imageswith said two dimensional image to create a three dimensional virtualmicroscope slide.
 2. The system of claim 1, wherein the image viewingworkstation further comprises a Z-plane access module configured topresent to a user one or more Z-plane images of a Z-stack in response toa request from the user for said one or more Z-plane images.
 3. Thesystem of claim 2, wherein the image viewing workstation integrates thedisplay of one or more Z-plane images of a Z-stack into the display of atwo dimensional view of the entire slide.
 4. The system of claim 1,wherein the instruction from the image viewing workstation to the imageacquisition device includes a set of three dimensional scan parameterscomprising length, width and depth.
 5. The system of claim 4, whereinthe set of three dimensional scan parameters further comprises a numberof Z-planes and a spacing between Z-planes.
 6. A computer implementedmethod for creating and viewing three dimensional virtual microscopeslides, comprising: orienting a microscope slide on a stage of an imageacquisition device configured to scan the microscope slide and create adigital image of a specimen on the microscope slide; scanning a firsttwo dimensional image of the specimen at a first resolution; providingthe two dimensional image to an image viewing device; receiving a set ofrevisit parameters from the image viewing device, the set of revisitparameters comprising a first location; scanning a second twodimensional image of the specimen at the first location at a secondresolution that is higher than the first resolution; providing thesecond two dimensional image to the image viewing device; receiving aset of three dimensional scan parameters from the image viewing device,the set of revisit parameters comprising a length, width, and depth;scanning a three dimensional Z-stack in accordance with the length,width, and depth, the Z-stack comprising a plurality of Z-plane images,each Z-plane image corresponding to a portion of the specimen in saiddepth; and storing the two dimensional image and the three dimensionalZ-stack together as a three dimensional virtual microscope slide.
 7. Themethod of claim 6, further comprising presenting the three dimensionalvirtual microscope slide on the display of an image viewing workstation.8. The method of claim 7, further comprising presenting one or moreZ-plane images of a Z-stack on the display of the image viewingworkstation in response to a request for said one or more Z-planeimages.
 9. The method of claim 8, further comprising integrating thepresentation of one or more Z-plane images of a Z-stack into thepresentation of a two dimensional view of the entire slide.
 10. A systemfor creating and viewing three dimensional virtual microscope slides,comprising: an image acquisition device configured to scan a microscopeslide and create a digital image of a specimen on the microscope slide,wherein portions of said digital image comprise a Z-stack including aplurality of images from the specimen that create a three dimensionalvirtual microscope slide; an image data server communicatively coupledwith the image acquisition device, the image data server configured toreceive a three dimensional virtual microscope slide from the imageacquisition device, store the three dimensional virtual microscopeslide, and provide image data from the three dimensional virtualmicroscope slide upon request; an image viewing workstationcommunicatively coupled with the image acquisition device and the imagedata server, the image viewing workstation configured to interpolate anddisplay an image at a first focus depth level in a Z-stack, wherein saidfirst focus depth level does not correspond to the focus depth level ofany of the plurality of images in the Z-stack.
 11. A computerimplemented method for creating and viewing three dimensional virtualmicroscope slides, comprising: scanning a two dimensional image of aspecimen at a high resolution; receiving a set of three dimensional scanparameters comprising length, width, and depth; scanning a threedimensional Z-stack in accordance with the length, width, and depth, theZ-stack comprising a plurality of Z-plane images wherein each Z-planeimage corresponds to a portion of the specimen in said depth; combiningthe two dimensional image and the Z-stack to form a three dimensionalvirtual microscope slide image; storing the three dimensional virtualmicroscope slide; interpolating a first Z-plane image that does notcorrespond to any Z-plane image in the Z-stack; and providing the firstZ-plane image to an image viewing device.